SCD affects approximately 90,000 individuals, primarily African-Americans, in the United States. SCD patients suffer frequent recurrent pain crises precipitated by vaso-occlusion. The pain crises often result in serious complications leading to high morbidity and mortality in moderately to severely affected SCD patients. The only treatment option currently available to SCD patients is the FDA approved drug hydroxyurea (HU). Selexys is developing SelG1, a first in class humanized anti-P-selectin antibody, for the prophylactic treatment of vaso-occlusive sickle cell-related pain crisis in patients with SCD. The treatment goal is to prevent or reduce the frequency and duration of sickle cell-related pain crises. According to the applicant, preclinical data in mouse models of SCD have demonstrated a P-selectin dependent mechanism of cell adhesion between sickled red cells, activated endothelium, leukocytes and platelets that precipitates vaso-occlusion. In these models, administration of an anti-P-selectin antibody, or genetic deletion of P-selectin, prevents vaso-occlusion, supporting the rationale for blocking P-selectin in SCD patients. The applicant has completed a Phase 1 study using SelG1 in normal human volunteers that demonstrated that SelG1 was safe and well tolerated up to a multi-dose cohort of 8mg/kg. SelG1 was shown to have pharmacologic properties that support a once-monthly dosing strategy. Selexys proposes a Phase 2 study to assess the efficacy of SelG1 at high and low doses compared to placebo and obtain important safety and tolerability data on the chronic dosing of SelG1. The primary aim of this Phase 2 safety and efficacy study is to evaluate SelG1 as a prophylactic therapy to reduce or prevent the ongoing frequency and duration of sickle cell-related pain crises. Selexys was granted orphan drug designation status in July 2008 for SelG1 for the treatment of vaso-occlusive crisis in patient with SCD.
Selexys Pharmaceuticals is a clinical development stage company advancing antibody-based drugs to treat inflammatory and thrombotic disease. Selexys lead program is a humanized anti-P-selectin antibody called SelG1 for the treatment of vasoocclusive sickle cell-related pain crisis in patients with sickle cell disease (SCD). SCD is an orphan indication with major unmet medical needs that affects approximately 90,000 individuals, primarily of African-Americans, in the US. SCD patients suffer frequent recurrent pain crisis precipitated by vasoocclusion resulting in serious complications leading to high morbidity and mortality in moderate to severe patients. The only treatment option is the FDA approved drug hydroxyurea, a repurposed cancer drug that has low compliance and is only effective in about 25% of patients that maintain compliance. Hematologists and SCD patients seek an alternative treatment option. Selexys seeks to fill that need with a first in class biologic therapeutic, a humanized antibody called SelG1 directed against the cell adhesion protein P-selectin. The clinical aim of this proposal is aligned with the goals and mission of the Food and Drug Administration, Office of Orphan Products Development to advance development of products that show promise for the treatment of rare diseases. Sickle cell disease is an orphan indication. Selexys was granted orphan status on July 22, 2008 for a humanized anti-P-selectin antibody for the treatment of vasoocclusive crisis in sickle cell disease (ODD #08-2597). Selexys has advanced the SelG1 program through preclinical studies, IND and conduct of a Phase I safety study in normal human volunteers. The Company has initiated work to conduct a first in-patient SelG1 Phase II safety and efficacy study expected to commence in June 2013. The Research Plan submitted with this application presents the data and conclusions that support the design and rationale for conducting the planned Phase II Study. [Selexys initiated the SelG1 Phase II Study, called SUSTAIN, on Aug. 19, 2013. The Study is ongoing.]